Vascular Calcification Revisited: A New Perspective for Phosphate Transport

Elevated serum phosphorus has emerged as a key risk factor for pathologic calcification of cardiovascular structures, or vascular calcification (VC). To prevent the formation of calciumphosphate deposits (CPD), the body uses adenosine-5’-triphosphate (ATP) to synthesize inhibitors of calcification, including proteins and inhibitors of low molecular weight. Extracellular pyrophosphate (PPi) is a potent inhibitor of VC, which is produced during extracellular hydrolysis of ATP. Loss of function in the enzymes and transporters that are involved in the cycle of extracellular ATP, including Pi transporters, leads to excessive deposition of calcium-phosphate salts. Treatment of hyperphosphatemia with Pi-binders and Injection of exogenous PPi are the effective treatments to prevent CPD in the aortic wall. The role of sodium phosphate cotransporters in ectopic calcification is contradictory and not well defined, but their important role in the control of intracellular Pi levels and the synthesis of ATP make them an important target to study.